Nebulization of Endotoxin during Mechanical Ventilation

Abstract

Gram-negative sepsis is the most common setting in the ICU in which abnormalities in lung function known as the Adult Respiratory distress Syndrome (ARDS) develops¹. Lipo-polysaccharide molecules residing in the outer membrane of gram-negative bacteria (endotoxins), are the bacterial components presumed to elicit the inflammatory response of the host that underlie the etiology of ARDS. ARDS is associated with significant abnormalities of lung mechanics^2,3. Decreased compliance with resultant rapid shallow breathing and increased deadspace ventilation, not refractory hypoxemia, are often rate-limiting factors preventing weaning from mechanical ventilation in patients with esthablished ARDS⁴. Decreases in compliance are also associated with increased airway pressure in the mechanically ventilated patient and with the development of macroscopic barotrauma⁵. The pathophysiology of lung injury induced by endotoxin has been studied extensively in vivo after intravenous or intraperitoneal infusion of endotoxin in a wide variety of animal models, using different methods and species, including the rat⁶, pig⁷, dog⁸ and sheep⁹. However, responses to intravenous infusion nearly always include symptoms of systemic involvement, with varying degrees of hemodynamic instability as a result. The same problem exist in other models of ARDS such as lung-lavage and oleic acid infusion. In order to produce a stable model in these instances, aggressive volume and inotropic support is usually necessary. As a result, treatment strategies under investigation are difficult to evaluate.